Clinical Trial of Mexiletine Hydrochloride for Spinal and Bulbar Muscular Atrophy (Med-SBMA)

A Multicenter, Randomized, Placebo-controlled, Double-blind Clinical Trial: The Efficacy and Safety of Mexiletine Hydrochloride for Amelioration of Motor Dysfunction in Spinal and Bulbar Muscular Atrophy

The purpose of this clinical trial is to evaluate the efficacy and safety of mexiletine hydrochloride in patients with spinal and bulbar muscular atrophy.

The main questions it aims to answer are:

Does mexiletine hydrochloride improve the ALSFRS-R score in spinal and bulbar muscular atrophy patients?

Participants will:

Take mexiletine hydrochloride or a placebo every day for 3 months Visit the hospital once every 4 weeks for evaluations.

Study Overview

• Status: Recruiting
• Conditions: Spinal and Bulbar Muscular Atrophy
• Intervention / Treatment: Drug: Mexiletine hydrochloride; Other: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 68
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Shinobu Shimizu, PhD; Phone Number: +81527442942; Email: shimizu.shinobu.w3@f.mail.nagoya-u.ac.jp
• Study Contact Backup: Name: Masahisa Katsuno, PhD, MD; Phone Number: +81527442389; Email: katsuno.masahisa.i1@f.mail.nagoya-u.ac.jp

Study Locations

• Japan
  • Bunkyo, Japan
    • Recruiting
    • Tokyo University Hospital
    • Contact: Tomotaka Yamamoto, PhD, MD; Phone Number: +81338155411; Email: yamatyama@gmail.com
  • Chiba, Japan
    • Recruiting
    • Chiba University Hospital
    • Contact: Kazumoto Shibuya, PhD, MD; Phone Number: +81432227171; Email: kazumoto@net.email.ne.jp
  • Sapporo, Japan
    • Recruiting
    • Hokkaido University Hospital
    • Contact: Ichiro Yabe, PhD, MD; Phone Number: +81117161161; Email: yabe@med.hokudai.ac.jp
  • Shimotsuke, Japan
    • Recruiting
    • Jichi Medical University Hospital
    • Contact: Mitsuya Morita, PhD, MD; Phone Number: +81285442111; Email: morita@jichi.ac.jp
  • Suita, Japan
    • Recruiting
    • Osaka University Hospital
    • Contact: Seiichi Nagano, PhD, MD; Phone Number: +81668795111; Email: nagano@neurol.med.osaka-u.ac.jp

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male patients with a CAG repeat count of 38 or more for the androgen receptor gene in genetic testing and a confirmed diagnosis of SBMA
2. Patients with muscle weakness (limb weakness and atrophy, or bulbar palsy) due to lower motor neuron lesion
3. Patients with a total ALSFRS-R score of ≥ 24 and ≤ 42 at screening
4. Patients who are at least 18 years old and less than 80 years old at the time of consent
5. Patients who give their voluntary written consent after having received adequate information on this study (However, if the patient is unable to sign the consent form due to the condition of the disease, a person equivalent to a regal representative must be present to provide written explanation, the prospective candidate must verbally consent to participate in the study, and a person equivalent to a regal representative must sign the consent form on behalf of the patient. The person who is to be the regal representative may sign the document on his/her behalf, noting the circumstances and his/her relationship to the subject.)

Exclusion Criteria:

1. Patients who have participated or are participating in a clinical trial within 12 weeks prior to enrollment
2. Patients with a history of hypersensitivity to any component of this drug product
3. Patients with a conduction disturbance (such as second- or third-degree atrioventricular block without a pacemaker, or left bundle branch block)
4. Patients with Brugada-type ECG
5. Patients with severe heart failure or heart disease (myocardial infarction, valvular disease, cardiomyopathy, etc.)
6. Patients with sinus bradycardia (<50 beats/minute)
7. Patients with systolic blood pressure of 90 mmHg or less
8. Patients with serum potassium level less than 3.5 mmol/L
9. Patients on antiarrhythmic drugs
10. Patients on antiepileptic drugs that affect to sodium channels
11. Patients on theophylline
12. Patients on narcotics
13. Patients who used Mexiletine within 1 month prior to enrollment or used Mexiletine for expectations of improvement in symptoms of SBMA
14. Patients with serious complications
15. Patients who cannot agree to use contraception during the study period
16. Other Patients deemed inappropriate by the investigator or subinvestigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo group	Other: Placebo; Placebo is administered orally divided into three times a day after meals for 12 weeks.
Active Comparator: Mexiletine group	Drug: Mexiletine hydrochloride; Mexiletine hydrochloride 300 mg is administered orally divided into three times a day after meals for 12 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) score	The ALSFRS-R is a comprehensive severity index comprising 12 items covering bulbar, upper limb, lower limb, and respiratory symptoms to evaluate the ADLs of patients with amyotrophic lateral sclerosis (ALS). Each item is rated on a five-point scale from 0 (worse) to 4 (better), and a total score (miniimum 0point and maximum 48 point) is calculated.	at 4weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ALSFRS-R Score	The ALSFRS-R is a comprehensive severity index comprising 12 items covering bulbar, upper limb, lower limb, and respiratory symptoms to evaluate the ADLs of patients with ALS. Each item is rated on a five-point scale from 0 (worse) to 4 (better), and a total score (miniimum 0point and maximum 48 point) is calculated.	up to 12 weeks
Spinal and Bulbar Muscular Atrophy Functional Rating Scale (SBMAFRS) score	The SBMAFRS is a disease-specific motor function assessment scale for Spinal and Bulbar Muscular Atrophy (SBMA).The SBMAFRS is a comprehensive severity index comprising 14 items covering bulbar, upper limb, lower limb, and respiratory symptoms to evaluate the ADLs of patients. Each item is rated on a five-point scale from 0 (worse) to 4 (better), and a total score (miniimum 0point and maximum 56 point) is calculated.	up to 12 weeks
Grip strength	Grip strength (kg) is set to evaluate the upper limb motor function of patients with SBMA.	up to 12 weeks
Tongue pressure	Tongue pressure (kPa) is set to evaluate the bulbar function of patients with SBMA.	up to 12 weeks
Timed walk test (4.6 meters)	The timed walk test (4.6 meters) is an evaluation index for muscle weakness and atrophy of the lower limbs that measures the walking time (in seconds).	up to 12 weeks
6-minute walk test	The 6-minute walk test is an evaluation index for lower limb muscle weakness and muscle atrophy that measures the walking distance (in meters).	up to 12 weeks
Respiratory function test (Forced Vital Capacity (FVC))	FVC (actual value (L) and predicted rate (%) (%FVC)) is set to evaluate for respiratory function.	up to 12 weeks
Respiratory function test (Peak Expiratory Flow (PEF))	PEF (actual value (L/sec) and predicted rate (%) (%PEF)) is set to evaluate for respiratory function.	up to 12 weeks

Collaborators and Investigators

• Sponsor: Masahisa Katsuno
• Investigators: Principal Investigator: Masahisa Katsuno, PhD, MD, Nagoya University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 28, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: February 26, 2025
• First Submitted That Met QC Criteria: March 3, 2025
• First Posted (Actual): March 6, 2025

Study Record Updates

• Last Update Posted (Actual): April 16, 2025
• Last Update Submitted That Met QC Criteria: April 11, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neurologic Manifestations; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Manifestations; Pathological Conditions, Anatomical; Neuromuscular Diseases; Genetic Diseases, Inborn; Neurodegenerative Diseases; Heredodegenerative Disorders, Nervous System; Genetic Diseases, X-Linked; Spinal Cord Diseases; Motor Neuron Disease; Muscular Atrophy, Spinal; Atrophy; Muscular Atrophy; Bulbo-Spinal Atrophy, X-Linked; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Membrane Transport Modulators; Mexiletine
• Other Study ID Numbers: CAMCR-026; jRCT2041240174 (Other Identifier: Japan Registry of Clinical Trials)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: If the principal investigator, clinical trial office, main stakeholder conclude that secondary use of individual data obtained in this clinical trial is beneficial for additional analysis, the secondary use of data excluding personal information will be acceptable after publication of results.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No